EA038337B1 - Ингибиторы ezh2 для лечения лимфомы - Google Patents
Ингибиторы ezh2 для лечения лимфомы Download PDFInfo
- Publication number
- EA038337B1 EA038337B1 EA201692285A EA201692285A EA038337B1 EA 038337 B1 EA038337 B1 EA 038337B1 EA 201692285 A EA201692285 A EA 201692285A EA 201692285 A EA201692285 A EA 201692285A EA 038337 B1 EA038337 B1 EA 038337B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- ezh2
- subject
- nhl
- lymphoma
- treatment
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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US201462013522P | 2014-06-17 | 2014-06-17 | |
US201462036265P | 2014-08-12 | 2014-08-12 | |
PCT/US2015/036310 WO2015195848A1 (en) | 2014-06-17 | 2015-06-17 | Ezh2 inhibitors for treating lymphoma |
Publications (3)
Publication Number | Publication Date |
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EA201692285A1 EA201692285A1 (ru) | 2017-06-30 |
EA201692285A8 EA201692285A8 (ru) | 2018-01-31 |
EA038337B1 true EA038337B1 (ru) | 2021-08-11 |
Family
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EA201692285A EA038337B1 (ru) | 2014-06-17 | 2015-06-17 | Ингибиторы ezh2 для лечения лимфомы |
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US (5) | US10166238B2 (ko) |
EP (2) | EP4252851A3 (ko) |
JP (1) | JP6779793B2 (ko) |
KR (2) | KR102497728B1 (ko) |
CN (2) | CN113289022A (ko) |
AU (3) | AU2015277139A1 (ko) |
BR (1) | BR112016029492A2 (ko) |
CA (1) | CA2952074C (ko) |
DK (1) | DK3157527T3 (ko) |
EA (1) | EA038337B1 (ko) |
ES (1) | ES2948442T3 (ko) |
FI (1) | FI3157527T3 (ko) |
HU (1) | HUE062158T2 (ko) |
IL (3) | IL285201B2 (ko) |
LT (1) | LT3157527T (ko) |
MX (2) | MX2021007651A (ko) |
PL (1) | PL3157527T3 (ko) |
PT (1) | PT3157527T (ko) |
SG (2) | SG11201610273VA (ko) |
SI (1) | SI3157527T1 (ko) |
WO (1) | WO2015195848A1 (ko) |
Families Citing this family (20)
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---|---|---|---|---|
WO2011160206A1 (en) | 2010-06-23 | 2011-12-29 | Morin Ryan D | Biomarkers for non-hodgkin lymphomas and uses thereof |
IL282741B2 (en) | 2013-12-06 | 2024-01-01 | Epizyme Inc | Tazematostat in combination with an acceptable treatment factor for use in the treatment of cancer |
MX2021007651A (es) * | 2014-06-17 | 2021-08-11 | Epizyme Inc | Inhibidores de ezh2 para tratar linfomas. |
CA2963149A1 (en) | 2014-10-16 | 2016-04-21 | Epizyme, Inc. | Method for treating cancer |
AU2015350108B2 (en) * | 2014-11-17 | 2021-04-08 | Eisai R&D Management Co., Ltd. | Method for treating cancer |
TW201636344A (zh) | 2014-12-05 | 2016-10-16 | 美國禮來大藥廠 | Ezh2抑制劑 |
EA201792304A1 (ru) | 2015-04-20 | 2018-03-30 | Эпизайм, Инк. | Комбинированная терапия для лечения рака |
CN107635965A (zh) | 2015-06-10 | 2018-01-26 | Epizyme股份有限公司 | 用于治疗淋巴瘤的ezh2抑制剂 |
US10493076B2 (en) | 2015-08-24 | 2019-12-03 | Epizyme, Inc. | Method for treating cancer |
TW201718598A (zh) | 2015-08-27 | 2017-06-01 | 美國禮來大藥廠 | Ezh2抑制劑 |
AU2017211331A1 (en) * | 2016-01-29 | 2018-06-07 | Epizyme, Inc. | Combination therapy for treating cancer |
WO2017210395A1 (en) | 2016-06-01 | 2017-12-07 | Epizyme, Inc. | Use of ezh2 inhibitors for treating cancer |
WO2017218953A1 (en) | 2016-06-17 | 2017-12-21 | Epizyme, Inc. | Ezh2 inhibitors for treating cancer |
CN110475557B (zh) * | 2017-01-20 | 2023-06-20 | 星座制药公司 | 固体分散体 |
WO2018183885A1 (en) | 2017-03-31 | 2018-10-04 | Epizyme, Inc. | Combination therapy for treating cancer |
JP2020522687A (ja) | 2017-06-02 | 2020-07-30 | エピザイム,インコーポレイティド | 癌を処置するためのezh2阻害剤の使用 |
US20210161883A1 (en) * | 2017-07-10 | 2021-06-03 | Constellation Pharmaceuticals, Inc. | Ezh2 inhibitor-induced gene expression |
JP7399079B2 (ja) | 2017-09-05 | 2023-12-15 | エピザイム,インコーポレイティド | 癌を処置するための併用療法 |
CN110960525A (zh) * | 2019-11-26 | 2020-04-07 | 济南大学 | 新型eed-ezh2相互作用抑制剂的确定和评价 |
CN110950834A (zh) * | 2019-11-26 | 2020-04-03 | 济南大学 | 新型eed-ezh2相互作用小分子抑制剂的确定和评价 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013138361A1 (en) * | 2012-03-12 | 2013-09-19 | Epizyme, Inc. | Inhibitors of human ezh2, and methods of use thereof |
WO2014062720A2 (en) * | 2012-10-15 | 2014-04-24 | Epizyme, Inc. | Methods of treating cancer |
WO2014071109A1 (en) * | 2012-11-01 | 2014-05-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US7229774B2 (en) | 2001-08-02 | 2007-06-12 | Regents Of The University Of Michigan | Expression profile of prostate cancer |
US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
EP2614369B1 (en) | 2010-09-10 | 2016-02-03 | Epizyme, Inc. | Method for determining the suitability of inhibitors of human ezh2 in treatment |
EP3323820B1 (en) | 2011-02-28 | 2023-05-10 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
TW201733984A (zh) | 2011-04-13 | 2017-10-01 | 雅酶股份有限公司 | 經取代之苯化合物 |
JP2014534178A (ja) | 2011-09-30 | 2014-12-18 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 癌の処置方法 |
BR112014025508B1 (pt) | 2012-04-13 | 2020-11-17 | Eisai R&D Management Co., Ltd. | forma de sal de um inibidor de histona metiltransferase ezh2 humana |
IL289300B2 (en) | 2012-04-13 | 2024-05-01 | Epizyme Inc | Combined treatment for cancer |
WO2013173441A2 (en) | 2012-05-16 | 2013-11-21 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
MY180311A (en) | 2012-10-15 | 2020-11-28 | Epizyme Inc | Substituted benzene compounds |
US20140120083A1 (en) | 2012-11-01 | 2014-05-01 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
US20150283142A1 (en) | 2013-03-15 | 2015-10-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
EP2934531A4 (en) | 2012-12-19 | 2016-06-15 | Glaxosmithkline Llc | COMBINATION |
CA2894216A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | 1,4-pyridone compounds |
EP2935264B1 (en) | 2012-12-21 | 2017-10-18 | Epizyme, Inc. | 1,4-pyridone bicyclic heteroaryl compounds |
WO2014172044A1 (en) | 2013-03-15 | 2014-10-23 | Epizyme, Inc. | Substituted benzene compounds |
EP2970306A4 (en) | 2013-03-15 | 2016-08-03 | Epizyme Inc | SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS CONDENSED IN 6.5 |
RU2019134551A (ru) * | 2013-05-30 | 2019-11-22 | Инфинити Фармасьютикалз, Инк. | Лечение злокачественных опухолей с использованием модуляторов изоформ pi3-киназы |
US10150764B2 (en) | 2013-07-19 | 2018-12-11 | Epizyme, Inc. | Substituted benzene compounds |
EP3022195A2 (en) | 2013-07-19 | 2016-05-25 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
EP3055422B1 (en) | 2013-10-09 | 2018-11-14 | Roche Diagnostics GmbH | Methods and compositions for detecting a mutation in the human ezh2 gene |
EP4324525A3 (en) | 2013-10-16 | 2024-07-17 | Epizyme, Inc. | Hydrochloride salt form for ezh2 inhibition |
JP2016533364A (ja) | 2013-10-18 | 2016-10-27 | エピザイム,インコーポレイティド | 癌を処置する方法 |
IL282741B2 (en) | 2013-12-06 | 2024-01-01 | Epizyme Inc | Tazematostat in combination with an acceptable treatment factor for use in the treatment of cancer |
MX2021007651A (es) | 2014-06-17 | 2021-08-11 | Epizyme Inc | Inhibidores de ezh2 para tratar linfomas. |
CA2966336A1 (en) | 2014-11-06 | 2016-05-12 | Dana-Farber Cancer Institute, Inc. | Use of compositions modulating chromatin structure for graft versus host disease (gvhd) |
AU2015350108B2 (en) | 2014-11-17 | 2021-04-08 | Eisai R&D Management Co., Ltd. | Method for treating cancer |
JP6544507B2 (ja) | 2015-02-09 | 2019-07-17 | 日本精機株式会社 | ヘッドアップディスプレイ装置 |
CN107635965A (zh) | 2015-06-10 | 2018-01-26 | Epizyme股份有限公司 | 用于治疗淋巴瘤的ezh2抑制剂 |
KR20170095656A (ko) | 2016-02-15 | 2017-08-23 | 동부대우전자 주식회사 | 방열구조를 갖는 세탁기 |
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2015
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- 2015-06-17 EA EA201692285A patent/EA038337B1/ru unknown
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- 2015-06-17 PT PT158095406T patent/PT3157527T/pt unknown
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013138361A1 (en) * | 2012-03-12 | 2013-09-19 | Epizyme, Inc. | Inhibitors of human ezh2, and methods of use thereof |
WO2014062720A2 (en) * | 2012-10-15 | 2014-04-24 | Epizyme, Inc. | Methods of treating cancer |
WO2014071109A1 (en) * | 2012-11-01 | 2014-05-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
Non-Patent Citations (4)
Title |
---|
Dyer M.J.S. et al. (1990) A New Human B-Cell Non-Hodgkin's Lymphoma Cell Line (Karpas 422) Exhibiting Both t(14;18) and t(4;11) Chromosomal Transolcations, Blood 75: 709-714, Abstract; Table 2 * |
Hassan U. et al. (2012) Prognostic Sub-Grouping of Diffuse Large B-Cell Lymphomas into Germinal Centre And Post Germinal Centre Groups by Immunohistochemistry after 6 Cycles of Chemotherapy. Asian Pacific Journal of Cancer Prevention. 13: 1341-1347, Abstract; Table 1 * |
Knutson S.K. et al. (2014) Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma. Molecular Cancer Therapeutics 13: 842-854. Published online 21 February, 2014, Abstract; Pages 842-843; Figures 3&4 * |
View of NCT01897571 on 2014_03_27 on ClinicalTrials.gov Archive. Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With В Cell Lymphomas. [retrieved from internet on 9 July 2015] <URL: https://clinicaltrials.gov/archive/NCT01897571/2014_03_27> (published 27 March 2014) Brief Summary; Detailed Description * |
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